Project Summary: Kidney is a vital organ that by maintaining body fluid volume/composition maintains cardiovascular functions. Unfortunately kidney function reduces with age that contributes to cardiovascular disorders such as heart failure and myocardial infarction during aging. American aging population is increasing. It is projected that 72 million Americans will be 65 years and older by the year 2030. Considering increased vulnerability of the elderly for compromised kidney function and associated cardiovascular disorders, a major economic burden on the US healthcare system is inevitable. Despite past and ongoing research efforts, mechanisms contributing to reduced kidney function during aging remain largely unknown. Therefore, understanding mechanism(s) of age-related decline of kidney function is needed more than ever in order to identify new molecular therapeutic targets that can restore kidney function and reduce associated cardiovascular events in the elderly Americans. This proposal is a new step taken in that direction. Using aging rat model as well as kidney cell culture systems we propose to examine the interplay between transcriptional and mitochondrial systems. In particular the interaction between transcription factors Nrf2 and Sp1 and mitochondrial protein ATP-synthase will be examined. Our hypothesis is that the interaction between Nrf2, Sp1 and ATP-synthase is important for normal kidney function and loss/disruption of this key interaction contributes to decline in kidney function in aging. The expectation is that in future these molecules can be targeted therapeutically to restore kidney function and reduce associated cardiovascular events in aging.